@ARTICLE{10.3389/fnbeh.2014.00427, AUTHOR={Altabella, Luisa and Sbriccoli, Marco and Zoratto, Francesca and Poleggi, Anna and Vinci, Ramona and Lacivita, Enza and Leopoldo, Marcello and Laviola, Giovanni and Cardone, Franco and Canese, Rossella and Adriani, Walter}, TITLE={Differential responses to acute administration of a new 5-HT7-R agonist as a function of adolescent pre-treatment: phMRI and immuno-histochemical study}, JOURNAL={Frontiers in Behavioral Neuroscience}, VOLUME={8}, YEAR={2014}, URL={https://www.frontiersin.org/articles/10.3389/fnbeh.2014.00427}, DOI={10.3389/fnbeh.2014.00427}, ISSN={1662-5153}, ABSTRACT={LP-211 is a new, selective agonist of serotonin (5-hydroxytryptamine, 5-HT) receptor 7 (5-HT7-R), which is part of a neuro-transmission system with a proposed role in neural plasticity and in mood, cognitive and sleep regulation. Adolescent subchronic LP-211 treatment produces some persisting changes in rats' forebrain structural and functional parameters. Here, using pharmacological MRI (phMRI), we investigated the effect of acute administration with LP-211 (10 mg/kg i.p.), or vehicle, to adult rats previously exposed to the same drug (0.25 mg/kg/day for 5 days), or vehicle, during adolescence (44–48 post-natal days); histology and immuno-histochemistry were performed ex vivo to evaluate neuro-anatomical and physiological long-term adaptation to pharmacological pre-treatment. The phMRI signal reveals forebrain areas (i.e., hippocampus, orbital prefrontal cortex), activated in response to LP-211 challenge independently of adolescent pre-treatment. In septum and nucleus accumbens, sensitized activation was found in adolescent pre-treated rats but not in vehicle-exposed controls. Immuno-histochemical analyses showed marked differences in septum as long-term consequence of the adolescent pre-treatment: increased level of 5-HT7-R, increased number of 5-HT7-R positive cells, and enhanced astrocyte activation. For nucleus accumbens, immuno-histochemical analyses did not reveal any difference between adolescent pre-treated rats and vehicle-exposed controls. In conclusion, subchronic LP-211 administration during adolescence is able to induce persistent physiological changes in the septal 5-HT7-R expression and astrocyte response that can still be observed in adulthood. Data shed new insights into roles of 5-HT7-R for normal and pathologic behavioral regulations.} }